Allergy, Common Cold
Conditions
Keywords
Infectious rhinitis, nasal irrigation, perennial allergy
Brief summary
Healsea® Children is a seawater-based nasal spray supplemented with a natural Symbiofilm® extract (0.02%) isolated from marine bacteria. Symbiofilm has antibiofilm activity against various bacterial pathogens involved in respiratory tract infections.Healsea® Children is indicated in the cleaning and moistening of nasal mucosa during common cold and rhinitis for children above 6 years. This non interventional post-market clinical investigation aimed to confirm the benefit of Healsea® Children in real life setting in children with perennial allergy who are more prone to common cold.
Detailed description
Healsea® Children is a seawater-based nasal spray supplemented with a natural Symbiofilm® extract (0.02%) isolated from marine bacteria. Symbiofilm® is an exopolymeric composition with emulsifying properties, in vitro antibiofilm activity and detachment properties against various bacterial pathogens involved in respiratory tract infections. Symbiofilm® has no bacteriostatic nor bactericidal activities. Healsea® Children is indicated in the cleaning and moistening of nasal mucosa during common cold and rhinitis. The common cold is an acute viral infection of the upper respiratory tract, involving, to variable degrees, sneezing, nasal congestion and discharge (rhinorrhea), sore throat, cough, low-grade fever, headache, and malaise (1). It can be caused by members of several families of viruses; the most common are rhinoviruses. Acute viral rhinitis is generally self-limiting. In children where the illness is not self-limiting and extends beyond 7-10 days, many agree that a bacterial infection is likely (1). Bacterial over infections and progression to a chronic state are favoured by the formation of biofilms, which facilitate bacterial growth and persistence as well as reducing antibiotic efficacy (2-3). Allergic diseases may play a particular role in promoting the respiratory infection recurrences (4). The physiological immune response is impaired in allergic subjects and allergic inflammation favours predisposition to respiratory infections. Subjects with allergic disorders may have functional defect of type 1 immune response that is relevant in fighting infections (5-6). Allergic rhinitis (AR) may affect up to 40% of the paediatric population. Nasal symptoms are caused by exposure to an allergen to which a patient is sensitized. AR is characterized by typical nasal symptoms and immunoglobulin E (IgE) -mediated inflammation. The allergic inflammatory process releases many cytokines and other proinflammatory proteins. Inflammation caused by nasal allergy leads to obstruction, fluid accumulation and acute disease. If these diseases are unsuccessfully treated, a chronic state of inflammation, obstruction, and infection develops that can cause mucosal damage and, ultimately, chronic disease (7). For these reasons, the paediatric IgE-dependent allergic population that is more prone to common cold represents a suitable target for Healsea® Children (8-9). During this prospective post-market clinical investigation, IgE-dependent allergic children with early symptoms of infectious rhinitis will be followed, children being treated with Healsea® Children on top of common cold conventional therapies or with conventional therapies only (excluded nasal irrigation). Conventional therapies for non-complicated infectious rhinitis are symptomatic but are not without side effects. For example, decongestant use can increase blood pressure, antihistamine intake is associated with drowsiness. Healsea® Children represents an interesting alternative that can not only improve acute infectious rhinitis symptomatology but could also limit the complication and progression to chronic state. This non interventional post-market clinical investigation aimed to confirm the benefit of Healsea® Children in a real life setting in children with perennial allergy.
Interventions
DEVICEHealsea® Children
Children will be administered Healsea Children , one puff (1-2 sec) in each nostril twice a day for 10 days on top of conventional therapies, as needed
OTHERConventional therapies for common cold
Children will receive conventional therapies for common cold, nasal irrigation excluded (antipyretics, mucolytics, decongestants, antitussives, systemic and topical corticosteroids, antibiotics)
Sponsors
Lallemand Pharma AG
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
6 Years to 10 Years
Healthy volunteers
No
Inclusion criteria
1. Male/Female subjects ≥6 and ≤10-year-old 2. AsIgE (Allergy specific IgE) ≥ class 2 (RAST) or positive prick test for at least one perennial allergen 3. Acute infectious rhinitis/rhinosinusitis for ≤48h before trial entry 4. Patient presenting with fever ≥ 37.5 °C at screening 5. Symptoms of headache, muscle ache, chilliness, sore throat, blocked nose, runny nose, cough, sneezing with a total score ≤9 (according to a physician-rated symptom score; scale: 0 to 3 \[0: no symptom to 3: severe intensity\]) 6. At least one of these symptoms: sore throat, runny nose or blocked nose (i.e., with a score ≥1) 7. Written consent obtained from parent/legal guardians 8. Written assent obtained from patient
Exclusion criteria
1. Known hypersensitivity/allergy to any component of the test device 2. Medical history that is considered by the investigator as a reason for non-inclusion, 3. Severe nasal septum deviation or other condition that could cause nasal obstruction such as the presence of nasal polyps 4. History of nasal or sinus surgery that in the opinion of the investigator may influence symptom scores 5. Antibiotic intake within 2 weeks before screening 6. Systemic corticosteroids within 4 weeks before screening 7. Antihistamines intake for allergy when treatment was started from less than 4 weeks 8. Bacterial lysate intake within 6 months before screening 9. Chronic decongestant use 10. Recent (within the previous 2 days) intake of a common cold medicine that in the opinion of the investigator may influence symptom score at screening (NSAID, nasal decongestants, cough medicines)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AUC (Area Under Curve) of the Wisconsin Upper Respiratory Symptoms Survey for Kids (WURSS-K) During the 10-day Treatment Period | Cumulative AUC of the WURSS score assessed from Day 1 to Day 10 | The WURSS-K will be assessed once daily, from Day1 to Day10 (treatment period) WURSS-K is a 3-dimensional structure questionnaire specifically designed for children 4 to 10 years of age. It includes 6 items assessing symptoms (symptoms score: runny nose, stuffy nose, sneezing, sore throat, cough, feeling tired), 7 items assessing functional impairments (quality of life score: think, sleep, breathe, talk, walk/climb stairs/exercise, go to school, play with friends), 1 item assessing global severity. All these items are scored from 0 (absent or no impairment) through 1 (a little bad), 2 (bad) and 3 (very bad). The AUC value of the WURSS-K during the 10 day- treatment period is comprised between 0 WURSS-K score\*day (no impairement) and 420 WURSS-K score \*day (maximal impairement) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Days With Stuffy Nose | Number of days with stuffy nose during the 10-day treatment period and a follow-up period of 20 days, up to 30 days | During the treatment period, the WURSS-K will be assessed once daily. After D10, the WURSS-K will be assessed once daily until the subject feels not sick for two consecutive days. Items 2 to 7 will be used to assess the duration of each common cold symptoms in both groups. Stuffy nose is the item 3. |
| Number of Days With Sneezing | Number of days with sneezing during the 10-day treatment period and a follow-up of 20 days, up to 30 days | During the treatment period, the WURSS-K will be assessed once daily. After D10, the WURSS-K will be assessed once daily until the subject feels not sick for two consecutive days. Items 2 to 7 will be used to assess the duration of common cold symptoms in both groups. Sneezing is the item 4. |
| Number of Days With Sore Throat | Number of days with sore throat during the 10-day treatment period and a follow-up of 20 days, up to 30 days | During the treatment period, the WURSS-K will be assessed once daily. After D10, the WURSS-K will be assessed once daily until the subject feels not sick for two consecutive days. Items 2 to 7 will be used to assess the duration of each common cold symptoms in both groups. Sore throat is the item 5. |
| Number of Days With Runny Nose | Number of days with runny nose during the 10-day treatment period and a follow-up of 20 days, up to 30 days | During the treatment period, the WURSS-K will be assessed once daily. After D10, the WURSS-K will be assessed once daily until the subject feels not sick for two consecutive days. Items 2 to 7 will be used to assess the duration of each common cold symptoms in both groups. Runny nose is the item 2 |
| Number of Days With Feeling Tired | Number of days with feeling tired during the 10-day treatment period and a follow-up of 20 days, up to 30 days | During the treatment period, the WURSS-K will be assessed once daily. After D10, the WURSS-K will be assessed once daily until the subject feels not sick for two consecutive days. Items 2 to 7 will be used to assess the duration of each common cold symptoms in both groups. Feeling tired is the item 7. |
| Respiratory Complication Requiring Antibiotic Prescription After the10-day Treatment Period | Number of subjects with respiratory complications during the 20-day follow-up period | The number of subjects who develop respiratory complication requiring antibiotic prescription during a 20-day follow-up period after the treatment period will be assessed in both groups and compared |
| Number of Participants With Use of Concomitant Treatments | During 10-day treatment period and a follow-up period of 20 days, up to 30 days | Number of subjects who took at least one concomitant treatment (antibiotics, antipyretics, systemic or local mucolytics, decongestants, antitussives, systemic and topical corticosteroids) that may impact symptoms of common cold and comparaison between groups |
| Number of Days With Cough | Number of days with cough during the 10-day treatment period and a follow-up of 20 days, up to 30 days | During the treatment period, the WURSS-K will be assessed once daily. After D10, the WURSS-K will be assessed once daily until the subject feels not sick for two consecutive days. Items 2 to 7 will be used to assess the duration of each common cold symptoms in both groups. Cough is the item 6. |
Countries
Poland
Participant flow
Recruitment details
Participants were outpatients visiting a physician in Polish hospitals or private practices at the onset of a common cold. The first patient was screened and enrolled on 14th of February 2022 and the last patient on 20th October 2022.
Participants by arm
| Arm | Count |
|---|---|
| Healsea® Children: Isotonic Seawater Based Nasal Spray Supplemented With Natural Symbiofilm® Extract Children will receive Healsea® Children nasal spray on top of conventional therapies for common cold, as needed.
Healsea® Children: Children will be administered Healsea Children , one puff (1-2 sec) in each nostril twice a day for 10 days on top of conventional therapies, as needed
Conventional therapies for common cold: Children will receive conventional therapies for common cold, nasal irrigation excluded (antipyretics, mucolytics, decongestants, antitussives, systemic and topical corticosteroids, antibiotics) | 101 |
| Conventional Therapies Children will receive conventional therapies for common cold as needed, nasal irrigation excluded
Conventional therapies for common cold: Children will receive conventional therapies for common cold, nasal irrigation excluded (antipyretics, mucolytics, decongestants, antitussives, systemic and topical corticosteroids, antibiotics) | 85 |
| Total | 186 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 10 |
| Overall Study | Protocol Violation | 1 | 0 |
Baseline characteristics
| Characteristic | Conventional Therapies | Total | Healsea® Children: Isotonic Seawater Based Nasal Spray Supplemented With Natural Symbiofilm® Extract |
|---|---|---|---|
| Age, Continuous | 8.02 Years STANDARD_DEVIATION 1.4 | 7.93 Years STANDARD_DEVIATION 1.41 | 7.86 Years STANDARD_DEVIATION 1.42 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 85 Participants | 186 Participants | 101 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Poland | 85 participants | 186 participants | 101 participants |
| Sex: Female, Male Female | 36 Participants | 81 Participants | 45 Participants |
| Sex: Female, Male Male | 49 Participants | 105 Participants | 56 Participants |
| Symptoms of acute rhinitis at baseline Blocked nose | 1.6 units on a scale STANDARD_DEVIATION 0.8 | 1.7 units on a scale STANDARD_DEVIATION 0.7 | 1.7 units on a scale STANDARD_DEVIATION 0.7 |
| Symptoms of acute rhinitis at baseline Chiliness | 0.3 units on a scale STANDARD_DEVIATION 0.5 | 0.2 units on a scale STANDARD_DEVIATION 0.5 | 0.2 units on a scale STANDARD_DEVIATION 0.4 |
| Symptoms of acute rhinitis at baseline Cough | 1.1 units on a scale STANDARD_DEVIATION 1 | 1.0 units on a scale STANDARD_DEVIATION 0.9 | 0.9 units on a scale STANDARD_DEVIATION 0.8 |
| Symptoms of acute rhinitis at baseline Headache | 0.5 units on a scale STANDARD_DEVIATION 0.6 | 0.6 units on a scale STANDARD_DEVIATION 0.6 | 0.6 units on a scale STANDARD_DEVIATION 0.6 |
| Symptoms of acute rhinitis at baseline Muscle ache | 0.2 units on a scale STANDARD_DEVIATION 0.5 | 0.2 units on a scale STANDARD_DEVIATION 0.4 | 0.1 units on a scale STANDARD_DEVIATION 0.4 |
| Symptoms of acute rhinitis at baseline Runny nose | 1.5 units on a scale STANDARD_DEVIATION 0.7 | 1.5 units on a scale STANDARD_DEVIATION 0.7 | 1.5 units on a scale STANDARD_DEVIATION 0.7 |
| Symptoms of acute rhinitis at baseline Sneezing | 0.9 units on a scale STANDARD_DEVIATION 0.7 | 1.0 units on a scale STANDARD_DEVIATION 0.7 | 1.0 units on a scale STANDARD_DEVIATION 0.7 |
| Symptoms of acute rhinitis at baseline Sore throat | 0.8 units on a scale STANDARD_DEVIATION 0.7 | 0.8 units on a scale STANDARD_DEVIATION 0.7 | 0.8 units on a scale STANDARD_DEVIATION 0.7 |
| Symptoms of acute rhinitis at baseline: temperature | 37.81 Degrees Celcius STANDARD_DEVIATION 0.39 | 37.78 Degrees Celcius STANDARD_DEVIATION 0.31 | 37.75 Degrees Celcius STANDARD_DEVIATION 0.23 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 101 | 0 / 85 |
| other Total, other adverse events | 17 / 101 | 23 / 85 |
| serious Total, serious adverse events | 0 / 101 | 0 / 85 |
Outcome results
Primary
AUC (Area Under Curve) of the Wisconsin Upper Respiratory Symptoms Survey for Kids (WURSS-K) During the 10-day Treatment Period
The WURSS-K will be assessed once daily, from Day1 to Day10 (treatment period) WURSS-K is a 3-dimensional structure questionnaire specifically designed for children 4 to 10 years of age. It includes 6 items assessing symptoms (symptoms score: runny nose, stuffy nose, sneezing, sore throat, cough, feeling tired), 7 items assessing functional impairments (quality of life score: think, sleep, breathe, talk, walk/climb stairs/exercise, go to school, play with friends), 1 item assessing global severity. All these items are scored from 0 (absent or no impairment) through 1 (a little bad), 2 (bad) and 3 (very bad). The AUC value of the WURSS-K during the 10 day- treatment period is comprised between 0 WURSS-K score\*day (no impairement) and 420 WURSS-K score \*day (maximal impairement)
Time frame: Cumulative AUC of the WURSS score assessed from Day 1 to Day 10
Population: All included subjects who used the investigational medical device at least once and with non-missing value at Day1 and at least another non-missing time point between Day2 and Day10. Otherwise, the AUC was missing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healsea® Children: Isotonic Seawater Based Nasal Spray Supplemented With Natural Symbiofilm® Extract | AUC (Area Under Curve) of the Wisconsin Upper Respiratory Symptoms Survey for Kids (WURSS-K) During the 10-day Treatment Period | 36.56 scores on WURSS-K scale* days | Standard Deviation 21.14 |
| Conventional Therapies | AUC (Area Under Curve) of the Wisconsin Upper Respiratory Symptoms Survey for Kids (WURSS-K) During the 10-day Treatment Period | 55.54 scores on WURSS-K scale* days | Standard Deviation 27.86 |
p-value: <0.05Wilcoxon (Mann-Whitney)
Secondary
Number of Days With Cough
During the treatment period, the WURSS-K will be assessed once daily. After D10, the WURSS-K will be assessed once daily until the subject feels not sick for two consecutive days. Items 2 to 7 will be used to assess the duration of each common cold symptoms in both groups. Cough is the item 6.
Time frame: Number of days with cough during the 10-day treatment period and a follow-up of 20 days, up to 30 days
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healsea® Children: Isotonic Seawater Based Nasal Spray Supplemented With Natural Symbiofilm® Extract | Number of Days With Cough | 6.1 Day | Standard Error 6.2 |
| Conventional Therapies | Number of Days With Cough | 7.1 Day | Standard Error 7.2 |
Comparison: For each item 2 to 7 of the WURSS-K questionnaire, the impact of the treatment chosen on the corresponding common cold symptom duration was analyzed by means of Cox model and p-value (Wald) calculatedp-value: 0.395495% CI: [0.83, 1.601]Regression, Cox
Secondary
Number of Days With Feeling Tired
During the treatment period, the WURSS-K will be assessed once daily. After D10, the WURSS-K will be assessed once daily until the subject feels not sick for two consecutive days. Items 2 to 7 will be used to assess the duration of each common cold symptoms in both groups. Feeling tired is the item 7.
Time frame: Number of days with feeling tired during the 10-day treatment period and a follow-up of 20 days, up to 30 days
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healsea® Children: Isotonic Seawater Based Nasal Spray Supplemented With Natural Symbiofilm® Extract | Number of Days With Feeling Tired | 4.8 Day | Standard Error 6.2 |
| Conventional Therapies | Number of Days With Feeling Tired | 6.4 Day | Standard Error 7.3 |
Comparison: For each item 2 to 7 of the WURSS-K questionnaire, the impact of the treatment chosen on the corresponding common cold symptom duration was analyzed by means of Cox model and p-value (Wald) calculatedp-value: 1.21895% CI: [0.871, 1.703]Regression, Cox
Secondary
Number of Days With Runny Nose
During the treatment period, the WURSS-K will be assessed once daily. After D10, the WURSS-K will be assessed once daily until the subject feels not sick for two consecutive days. Items 2 to 7 will be used to assess the duration of each common cold symptoms in both groups. Runny nose is the item 2
Time frame: Number of days with runny nose during the 10-day treatment period and a follow-up of 20 days, up to 30 days
Population: All included subjects who used the investigational medical device at least once
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healsea® Children: Isotonic Seawater Based Nasal Spray Supplemented With Natural Symbiofilm® Extract | Number of Days With Runny Nose | 7.4 Day | Standard Error 6.9 |
| Conventional Therapies | Number of Days With Runny Nose | 9.4 Day | Standard Error 7.9 |
Comparison: For each item 2 to 7 of the WURSS-K questionnaire, the impact of the treament chosen on the corresponding common cold symptom duration was analyzed by means of Cox model and p-value (Wald) calculatedp-value: 0.702695% CI: [0.778, 1.451]Regression, Cox
Secondary
Number of Days With Sneezing
During the treatment period, the WURSS-K will be assessed once daily. After D10, the WURSS-K will be assessed once daily until the subject feels not sick for two consecutive days. Items 2 to 7 will be used to assess the duration of common cold symptoms in both groups. Sneezing is the item 4.
Time frame: Number of days with sneezing during the 10-day treatment period and a follow-up of 20 days, up to 30 days
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healsea® Children: Isotonic Seawater Based Nasal Spray Supplemented With Natural Symbiofilm® Extract | Number of Days With Sneezing | 6.1 Day | Standard Error 6.5 |
| Conventional Therapies | Number of Days With Sneezing | 5.9 Day | Standard Error 6 |
Comparison: For each item 2 to 7 of the WURSS-K questionnaire, the impact of the treatment chosen on the corresponding common cold symptom duration was analyzed by means of Cox model and p-value (Wald) calculatedp-value: 0.959895% CI: [0.726, 1.356]Regression, Cox
Secondary
Number of Days With Sore Throat
During the treatment period, the WURSS-K will be assessed once daily. After D10, the WURSS-K will be assessed once daily until the subject feels not sick for two consecutive days. Items 2 to 7 will be used to assess the duration of each common cold symptoms in both groups. Sore throat is the item 5.
Time frame: Number of days with sore throat during the 10-day treatment period and a follow-up of 20 days, up to 30 days
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healsea® Children: Isotonic Seawater Based Nasal Spray Supplemented With Natural Symbiofilm® Extract | Number of Days With Sore Throat | 3.9 Day | Standard Error 5.6 |
| Conventional Therapies | Number of Days With Sore Throat | 5.2 Day | Standard Error 6.9 |
Comparison: For each item 2 to 7 of the WURSS-K questionnaire, the impact of the treatment chosen on the corresponding common cold symptom duration was analyzed by means of Cox model and p-value (Wald) calculatedp-value: 0.101695% CI: [0.945, 1.88]Regression, Cox
Secondary
Number of Days With Stuffy Nose
During the treatment period, the WURSS-K will be assessed once daily. After D10, the WURSS-K will be assessed once daily until the subject feels not sick for two consecutive days. Items 2 to 7 will be used to assess the duration of each common cold symptoms in both groups. Stuffy nose is the item 3.
Time frame: Number of days with stuffy nose during the 10-day treatment period and a follow-up period of 20 days, up to 30 days
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healsea® Children: Isotonic Seawater Based Nasal Spray Supplemented With Natural Symbiofilm® Extract | Number of Days With Stuffy Nose | 6.8 Day | Standard Error 6.3 |
| Conventional Therapies | Number of Days With Stuffy Nose | 8.6 Day | Standard Error 7.5 |
Comparison: For each item 2 to 7 of the WURSS-K questionnaire, the impact of the treatment chosen on the corresponding common cold symptom duration was analyzed by means of Cox model and p-value (Wald) calculatedp-value: 0.632295% CI: [0.792, 1.469]Regression, Cox
Secondary
Number of Participants With Use of Concomitant Treatments
Number of subjects who took at least one concomitant treatment (antibiotics, antipyretics, systemic or local mucolytics, decongestants, antitussives, systemic and topical corticosteroids) that may impact symptoms of common cold and comparaison between groups
Time frame: During 10-day treatment period and a follow-up period of 20 days, up to 30 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Healsea® Children: Isotonic Seawater Based Nasal Spray Supplemented With Natural Symbiofilm® Extract | Number of Participants With Use of Concomitant Treatments | 53 participants |
| Conventional Therapies | Number of Participants With Use of Concomitant Treatments | 66 participants |
p-value: 0.00195% CI: [0.174, 0.644]Regression, Logistic
Secondary
Respiratory Complication Requiring Antibiotic Prescription After the10-day Treatment Period
The number of subjects who develop respiratory complication requiring antibiotic prescription during a 20-day follow-up period after the treatment period will be assessed in both groups and compared
Time frame: Number of subjects with respiratory complications during the 20-day follow-up period
Population: FAS
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Healsea® Children: Isotonic Seawater Based Nasal Spray Supplemented With Natural Symbiofilm® Extract | Respiratory Complication Requiring Antibiotic Prescription After the10-day Treatment Period | 1 Participants |
| Conventional Therapies | Respiratory Complication Requiring Antibiotic Prescription After the10-day Treatment Period | 2 Participants |
Comparison: The impact of the treatment chosen on the risk to develop respiratory complication requiring antibiotic prescription during a 20-day follow-up was analyzed by a multivariate logistic modelp-value: >0.05Regression, Logistic